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Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion

Russo

Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion Thumbnail


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Abstract

Proteases of the malaria parasite Plasmodium falciparum have long been investigated as drug targets. The P. falciparum genome encodes 10 aspartic proteases called plasmepsins, which are involved in diverse cellular processes. Most have been studied extensively but the functions of plasmepsins IX and X (PMIX and PMX) were unknown. Here we show that PMIX is essential for erythrocyte invasion, acting on rhoptry secretory organelle biogenesis. In contrast, PMX is essential for both egress and invasion, controlling maturation of the subtilisin-like serine protease SUB1 in exoneme secretory vesicles. We have identified compounds with potent antimalarial activity targeting PMX, including a compound known to have oral efficacy in a mouse model of malaria.

Citation

Russo. (2017). Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion. Science, 518 - 522. https://doi.org/10.1126/science.aan1478

Acceptance Date Sep 18, 2017
Publication Date Oct 27, 2017
Journal Science
Print ISSN 0036-8075
Publisher American Association for the Advancement of Science
Pages 518 - 522
DOI https://doi.org/10.1126/science.aan1478
Publisher URL https://science.sciencemag.org/content/358/6362/518/tab-article-info

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